The presence of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). We conducted a prospective, single-arm, phase II study in adults with B-cell ALL with MRD ≥1 × 10⁻⁴ after ≥3 months from the start of frontline therapy or one month from any salvage therapy. Blinatumomab was administered at a standard dosing of 28 micrograms daily as a continuous infusion for up to five cycles and up to four additional maintenance cycles. Thirty-seven patients with a median age of 43 years (range, 22–84 years) were treated. Twenty-seven patients (73%) were treated in first complete remission (CR) and 10 patients (27%) in second CR and beyond. Eighteen patients (49%) had Philadelphia-chromosome positive ALL and received concomitant tyrosine kinase inhibitor therapy. Twenty-three patients (62%) had a baseline MRD ≥10⁻³. A median of three cycles (range, 1–9 cycles) were administered. Overall, 27 patients (73%) achieved MRD-negative remission. With a median follow-up of 31 months (range, 5–70 months), the estimated 3-year relapse-free survival (RFS) rate was 63% (95% confidence interval [CI], 43%–77%) and overall survival (OS) rate 67% (95% CI, 46%–81%). These rates were 51% (95% CI, 27%–70%) and 61% (95% CI, 36%–78%) in patients with baseline MRD ≥1 × 10⁻³, and 83% (95% CI, 45%–95%) and 77% (95% CI, 32%–95%) in patients with baseline MRD <10⁻³ respectively. The rates of adverse events were consistent with previous studies of blinatumomab. In summary, blinatumomab induced MRD negativity in most patients and resulted in high rates of RFS and OS. This study is registered at www.clinicaltrials.gov as #NCT02458014. Funding was provided by Amgen Inc.

中文翻译：

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Blinatumomab 与 B 细胞谱系急性淋巴细胞白血病和阳性可测量残留病灶（阈值为 10-4 或更高）患者的良好结局相关

可测量的残留病灶 (MRD) 的存在是急性淋巴细胞白血病 (ALL) 复发的最强预测因子。^{我们在 MRD ≥ 1 × 10 -4}的 B 细胞 ALL 成年患者中进行了一项前瞻性、单组、II 期研究从前线治疗开始≥3 个月或从任何挽救治疗开始 1 个月后。Blinatumomab 以每天 28 微克的标准剂量作为连续输注给药，最多五个周期和最多四个额外的维持周期。37 名中位年龄为 43 岁（范围 22-84 岁）的患者接受了治疗。27 名患者 (73%) 在第一次完全缓解 (CR) 时接受治疗，10 名患者 (27%) 在第二次 CR 及以上接受治疗。18 名患者 (49%) 患有费城染色体阳性 ALL，并同时接受酪氨酸激酶抑制剂治疗。23 名患者 (62%) 的基线 MRD ≥10 ^-3. 施用了三个周期的中位数（范围，1-9 个周期）。总体而言，27 名患者 (73%) 实现了 MRD 阴性缓解。中位随访 31 个月（范围 5-70 个月），估计 3 年无复发生存率 (RFS) 为 63%（95% 置信区间 [CI]，43%-77%），总生存 (OS) 率为 67%（95% CI，46%–81%）。^{在基线 MRD ≥ 1 × 10 -3}的患者中，这些比率分别为 51%（95% CI，27%–70%）和 61%（95% CI，36%–78%），以及 83%（95% CI ， 45%–95%）和 77%（95% CI，32%–95%）在基线 MRD <10 ^{−3的患者中}分别。不良事件发生率与之前对博纳吐单抗的研究一致。总之，blinatumomab 在大多数患者中诱导了 MRD 阴性，并导致高 RFS 和 OS 率。本研究在 www.clinicaltrials.gov 注册为#NCT02458014。资金由安进公司提供。